The immune system protects the human body against infection as well as diseases such as cancer. An important aspect of the immune system is the adaptive immune response. The adaptive immune response is antigen-specific and allows for a targeted response against a specific pathogen or diseased cell. T cells play an essential role in this response due to their ability to recognize specific antigens through T cell receptors (TCR). The specificity of a T cell depends on the sequence of its TCR.
There is significant interest in genetically engineering T cells in order to target cancer cells. In one strategy, T cells are transduced with viral vectors encoding T cell receptors that recognize cancer-specific antigens. However, such immunotherapy techniques require the extraction, processing, and reintroduction of T cells from a patient's own blood, making the procedure time-consuming and expensive. In addition, because there are many circumstances where patients have very little of their own T cells available to be reprogrammed (e.g. patients with HIV infections), not all patients can benefit from such treatments.
There have been a number of efforts directed towards mass production of reprogrammed T cells using stem cell technology. For example, the generation of tumor-specific T cells from genetically modified hematopoietic stem cells obtained from the fetal liver or cord blood has been reported (see, e.g. Vatakis, et al. Proceedings of the National Academy of Sciences 2011, 108(51): E1408-E1416; Giannoni et al. Molecular Therapy 2013, 21(5): 1044-1054). In another study, retroviral vectors have been used to genetically program bone marrow cells for TCR engineering in mouse models (see, e.g. Yang, et al. Proceedings of the National Academy of Sciences of the United States of America 2005, 102(12): 4518-4523).
Because of the significant potential impact related to the utilization of antigen-specific T cells in treating tumors and cancer cells, there is a need for compositions and techniques that enable the mass production of T cells having defined antigen specificity. This invention addresses this and other needs in the art.